A number of therapeutic agents are known to produce abnormalities in carbohydrate metabolism in humans. The objective of this research is to elucidate the mechanisms through which these drugs produce the effect and to determine factors which may predispose man to drug-induced diabetes. One portion of the research is directed toward determination of the nature of chemical receptors on the pancreatic beta cell. For this purpose we intend to study the binding characteristics of the diabetogen, alloxan. High concentrations of D-glucose have been found to inhibit the effects of alloxan on pancreatic tissues. We will determine if this interaction is mediated through a glucose-induced blockade of alloxan binding to the beta cell membrane. We have also found that barbituric acid, prevents alloxan-induced diabetes in vivo. In vitro experiments have been planned to determine if the interaction between these two chemicals is at the level of the pancreatic beta cell. The second portion of the research is directed to an assessment of the pancreotoxic effects of environmental chemicals. Cadmium inhibits pancreatic insulin secretion. Our results suggest that this action is related to an inhibition of calcium uptake by the beta cells. In vitro experiments will be conducted to determine the effect of cadmium on glucose-and tolbutamide-induced calcium uptake by beta cells.